Identification of pesticides exposure biomarkers for residents living close to vineyards in France

Il existe de plus en plus de données indiquant que les personnes vivant près de cultures sont exposées aux pesticides utilisés sur ces cultures à travers notamment de phénomènes de dérive et de volatilisation des pesticides au-delà des zones traitées. Toutefois, ces données sont difficilement généralisables au contexte agricole français et il est donc nécessaire de produire des mesures objectives de l’exposition non professionnelle aux pesticides chez les personnes vivant près de cultures en France, en particulier près de vignes. La réalisation de mesures de biomarqueurs d’exposition dans des matrices biologiques est une approche pertinente pour produire de telles données. Toutefois, il existe plusieurs défis pour estimer l'exposition aux pesticides à partir de mesures biologiques, en particulier la sélection de biomarqueurs d’expositions permettant de refléter de manière fiable une exposition spécifique à des polluants de l’environnement, y compris dans un contexte d’expositions multisources. L'objectif de la thèse est de développer une approche d’identification des biomarqueurs d’exposition pertinents pour mesurer l’exposition aux pesticides utilisés spécifiquement dans les cultures viticoles et identifier les matrices biologiques les plus adaptées à leur dosage et à leur interprétation. Cette approche est basée sur des dosages biologiques ad hoc réalisés à partir d’échantillons biologiques (urines et cheveux) de 121 adultes et enfants inclus dans l’étude Esteban, entre 2014 et 2016, et vivant près ou loin de parcelles viticoles. Ces analyses ont concerné cinq pesticides prioritaires sélectionnés pour l’étude (folpel, mancozèbe, tébuconazole, glyphosate, cuivre) et leurs métabolites. Cette approche a permis d'identifier trois biomarqueurs d’exposition pertinents (métabolites du folpel et du tébuconazole) à la fois spécifiques des pesticides prioritaires utilisés dans les cultures viticoles en France et pertinents au regard des études antérieures visant à évaluer spécifiquement les expositions dans un contexte viticole. Les travaux réalisés dans le cadre de la thèse ont également permis d'identifier les stratégies analytiques les plus appropriées (matrices biologiques, méthodes analytiques) pour évaluer les expositions aux pesticides chez les personnes vivant près de vignes. Ces travaux sont une étape préalable pour fournir des indications sur les exigences et les implications pratiques d’une étude à grande échelle visant à caractériser l’exposition aux pesticides chez les riverains de vignes en France. Il s’agit d’une étape essentielle pour conduire des études épidémiologiques à grande échelle et des évaluations des risques sanitaires associés, mais également pour développer des stratégies de prévention et des politiques publiques appropriées.There is increasing evidence that people living near crops are exposed to the pesticides used on these crops, particularly through drift and volatilization of pesticides beyond the treated areas. However, these data are difficult to generalize to the French agricultural context and it is therefore necessary to produce objective measurements of non-occupational exposure to pesticides in people living near crops in France, in particular near vineyards. Measuring biomarkers of exposure in biological matrices is a relevant approach to produce such data. However, there are several challenges in estimating pesticide exposure from biological measurements, in particular the selection of exposure biomarkers that reliably reflect specific exposure to environmental pollutants, including in the context of multisource exposures. The objective of this thesis is to develop an approach to identify relevant biomarkers of exposure to measure exposure to pesticides used specifically in vineyards and to identify the most appropriate biological matrices for their measurement and interpretation. This approach is based on ad hoc bioassays performed on biological samples (urine and hair) from 121 adults and children included in the Esteban study, between 2014 and 2016, and living near or far from vineyard plots. These analyses concerned five priority pesticides selected for the study (folpet, mancozeb, tebuconazole, glyphosate, copper) and their metabolites. This approach allowed the identification of three relevant biomarkers of exposure (metabolites of folpet and tebuconazole) that are both specific to the priority pesticides used in wine-growing crops in France and relevant to previous studies aimed at specifically assessing exposure in a wine-growing context. The work carried out in the framework of the thesis also allowed the identification of the most appropriate analytical strategies (biological matrices, analytical methods) to evaluate pesticide exposures in people living near vineyards. This work is a preliminary step to provide guidance on the requirements and practical implications of a large-scale study to characterize pesticide exposure in people living near vineyards in France. This is an essential step for conducting large-scale epidemiological studies and assessments of the associated health risks, but also for developing prevention strategies and appropriate public policies

Recherche de biomarqueurs pour caractériser au mieux les expositions aux pesticides chez les riverains de zones viticoles

There is increasing evidence that people living near crops are exposed to the pesticides used on these crops, particularly through drift and volatilization of pesticides beyond the treated areas. However, these data are difficult to generalize to the French agricultural context and it is therefore necessary to produce objective measurements of non-occupational exposure to pesticides in people living near crops in France, in particular near vineyards. Measuring biomarkers of exposure in biological matrices is a relevant approach to produce such data. However, there are several challenges in estimating pesticide exposure from biological measurements, in particular the selection of exposure biomarkers that reliably reflect specific exposure to environmental pollutants, including in the context of multisource exposures. The objective of this thesis is to develop an approach to identify relevant biomarkers of exposure to measure exposure to pesticides used specifically in vineyards and to identify the most appropriate biological matrices for their measurement and interpretation. This approach is based on ad hoc bioassays performed on biological samples (urine and hair) from 121 adults and children included in the Esteban study, between 2014 and 2016, and living near or far from vineyard plots. These analyses concerned five priority pesticides selected for the study (folpet, mancozeb, tebuconazole, glyphosate, copper) and their metabolites. This approach allowed the identification of three relevant biomarkers of exposure (metabolites of folpet and tebuconazole) that are both specific to the priority pesticides used in wine-growing crops in France and relevant to previous studies aimed at specifically assessing exposure in a wine-growing context. The work carried out in the framework of the thesis also allowed the identification of the most appropriate analytical strategies (biological matrices, analytical methods) to evaluate pesticide exposures in people living near vineyards. This work is a preliminary step to provide guidance on the requirements and practical implications of a large-scale study to characterize pesticide exposure in people living near vineyards in France. This is an essential step for conducting large-scale epidemiological studies and assessments of the associated health risks, but also for developing prevention strategies and appropriate public policies.Il existe de plus en plus de données indiquant que les personnes vivant près de cultures sont exposées aux pesticides utilisés sur ces cultures à travers notamment de phénomènes de dérive et de volatilisation des pesticides au-delà des zones traitées. Toutefois, ces données sont difficilement généralisables au contexte agricole français et il est donc nécessaire de produire des mesures objectives de l’exposition non professionnelle aux pesticides chez les personnes vivant près de cultures en France, en particulier près de vignes. La réalisation de mesures de biomarqueurs d’exposition dans des matrices biologiques est une approche pertinente pour produire de telles données. Toutefois, il existe plusieurs défis pour estimer l'exposition aux pesticides à partir de mesures biologiques, en particulier la sélection de biomarqueurs d’expositions permettant de refléter de manière fiable une exposition spécifique à des polluants de l’environnement, y compris dans un contexte d’expositions multisources. L'objectif de la thèse est de développer une approche d’identification des biomarqueurs d’exposition pertinents pour mesurer l’exposition aux pesticides utilisés spécifiquement dans les cultures viticoles et identifier les matrices biologiques les plus adaptées à leur dosage et à leur interprétation. Cette approche est basée sur des dosages biologiques ad hoc réalisés à partir d’échantillons biologiques (urines et cheveux) de 121 adultes et enfants inclus dans l’étude Esteban, entre 2014 et 2016, et vivant près ou loin de parcelles viticoles. Ces analyses ont concerné cinq pesticides prioritaires sélectionnés pour l’étude (folpel, mancozèbe, tébuconazole, glyphosate, cuivre) et leurs métabolites. Cette approche a permis d'identifier trois biomarqueurs d’exposition pertinents (métabolites du folpel et du tébuconazole) à la fois spécifiques des pesticides prioritaires utilisés dans les cultures viticoles en France et pertinents au regard des études antérieures visant à évaluer spécifiquement les expositions dans un contexte viticole. Les travaux réalisés dans le cadre de la thèse ont également permis d'identifier les stratégies analytiques les plus appropriées (matrices biologiques, méthodes analytiques) pour évaluer les expositions aux pesticides chez les personnes vivant près de vignes. Ces travaux sont une étape préalable pour fournir des indications sur les exigences et les implications pratiques d’une étude à grande échelle visant à caractériser l’exposition aux pesticides chez les riverains de vignes en France. Il s’agit d’une étape essentielle pour conduire des études épidémiologiques à grande échelle et des évaluations des risques sanitaires associés, mais également pour développer des stratégies de prévention et des politiques publiques appropriées

Determination of biomarkers of exposure to boscalid, captan, folpel, mancozeb and tebuconazole in urine and hair samples

International audienceIn order to develop a tiered approach to identify relevant biomarkers and matrices for assessing pesticide exposure in residents living close to vineyards, five priority pesticides (boscalid, captan, folpel, mancozeb and tebuconazole) and their metabolites were analyzed in urine and hair samples from the biobank of a French national prevalence study conducted between 2014 and 2016. To do this, several analytical methods based on gas chromatography coupled with tandem mass spectrometry (GC/MS/MS) were developed by relying on the expertise of the laboratory and the scientific literature, in particular on a paper describing the use of gas chromatography-mass spectrometry for the determination in human urine samples of ethylene thiourea (ETU), a metabolite of mancozeb, after a supported liquid extraction followed by a derivatization step [1]. The main adaptations carried out as part of this study concerned:•the determination of ethylene urea (EU), another metabolite of mancozeb, at the same time as ETU in urine samples•the determination of all substances of interest including boscalid, EU and ETU, folpel and one of its metabolite (phthalimide), tebuconazole and one of its metabolite (hydroxytebuconazole), and tetrahydrophthalimide (metabolite of captan) in organic hair extracts by GC/MS/MS after a derivatization step

Pesticide exposures for residents living close to agricultural lands: A review

International audienceBackground - Residents living close to agricultural lands might be exposed to pesticides through non-occupational pathways including spray drift and volatilization of pesticides beyond the treated area. Objective - This review aimed to identify and analyze scientific literature measuring pesticide exposure in non-farmworker residents living close to agricultural lands, and to suggest practical implications and needs for future studies. Methods - A review was performed using inclusion criteria to identify original articles of interest published between 2003 and 2018. Results - From the 29 articles selected in this review, 2 belonged to the same study and were grouped, resulting in a total of 27 studies. Seven studies assessed exposure to pesticides using environmental samples, 13 collected biological samples and 7 analyzed both. Nine studies included a reference group of residents living far from agricultural lands while 11 assessed the influence of the spraying season or spray events on pesticide exposures. Studies included in this review provide evidence that residents living near to agricultural lands are exposed to higher levels of pesticides than residents living further away. Discussion and conclusion - This review highlights that the following study design characteristics may be more appropriate than others to measure pesticide spray drift exposure in non-farmworker residents living close to agricultural lands: inclusion of a non-agricultural control group, collection of both biological and environmental samples with repeated sampling, measurements at different periods of the year, selection of numerous study sites related to one specific crop group, and measurements of pesticides which are specific to agricultural use. However, few studies to date incorporate all these characteristics. Additional studies are needed to comprehensively measure non-occupational pesticide exposures in this population in order to evaluate health risks, and to develop appropriate prevention strategies

Maternal diet quality during pregnancy and biomarkers of potentially toxic trace element exposure: Data from the ELFE cohort

International audienceThe contribution of the diet to potentially toxic trace element exposure in pregnancy has been rarely addressed. The objective of the present study was to determine the association between the maternal diet during pregnancy and biomarkers of exposure for arsenic (As), mercury (Hg) and lead (Pb) at delivery. As was assessed in maternal urine, Hg in maternal hair, and Pb in cord blood, as a proxy for in utero exposure. Based on 2995 women from the ELFE nationwide birth cohort, higher scores for dietary patterns considered healthy were associated with higher concentrations of As and Hg in maternal matrices. Levels of cord blood Pb were inconsistently associated with dietary patterns considered healthy, and lower with a dietary pattern driven by milk and breakfast cereals. Lower levels of Hg were associated with higher Western dietary pattern scores. In conclusion, higher levels of maternal urinary As and hair Hg are associated with diets considered as “Healthy”, while cord blood Pb was not strongly correlated with dietary exposure

Identification of pesticides exposure biomarkers for residents living close to vineyards in France

International audienceBiomonitoring can be relevant for assessing pesticides exposure of residents living close to vineyards (LCTV). However, because xenobiotics are generally present at low levels in human biological matrices and the sources of pesticide exposure are multiple, several challenges need to be overcome to reliably assess exposure in residents LCTV. This includes particularly identifying the most appropriate exposure biomarkers, the biological matrices in which they should be measured, and analytical methods that are sufficiently sensitive and specific to quantify them. The aim of the present study was to develop a tiered approach to identify relevant biomarkers and matrices for assessing pesticide exposure in residents LCTV. We used samples from a biobank for 121 adults and children included in a national prevalence study conducted between 2014 and 2016 who lived near or far from vineyards. We analyzed five priority pesticides (folpet, mancozeb, tebuconazole, glyphosate, and copper) and their metabolites in urine and hair samples. We identified relevant biomarkers according to three criteria related to: i) the detection frequency of those pesticides and metabolites in urine and hair, ii) the difference in concentrations depending on residence proximity to vineyards and, iii) the influence of other environmental and occupational exposure sources on pesticide levels. This tiered approach helped us to identify three relevant metabolites (two metabolites of folpet and one of tebuconazole) that were quantified in urine, tended to be higher in residents LCTV than in controls, and were not significantly influenced by occupational, dietary, or household sources of pesticide exposure. Our approach also helped us to identify the most appropriate measurement strategies (biological matrices, analytical methods) to assess pesticide exposure in residents LCTV. The approach developed here was a prerequisite step for guiding a large-scale epidemiological study aimed at comprehensively measuring pesticides exposures in French residents LCTV with a view to developing appropriate prevention strategies

Association entre l’alimentation et des biomarqueurs d’exposition aux métaux lourds pendant la grossesse

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